Micro I-5,6: Innate Immunity

Front 1

Define innate immunity

Back 1

form of immunity that exist before exposure to pathogens; hard wired, rapid, and recognizes conserved patterns on pathogens called PAMPS

Front 2

4 major characteristics of innate immunity

Back 2

1. Limited repertoire of receptors 2. Ancient system 3. Intimately intertwined with the adaptive immune system 4.Invariant and constant

Front 3

What is the major cellular response of innate immunity?

Back 3

Inflammation or the Inflammatory response

Front 4

The 4 players that participate in the generation of inflammation

Back 4

Tissues, Early soluble mediators, cells, other soluble mediators

Front 5

What are the barriers to pathogen entry

Back 5

Physical (External skin and internal mucosa) & Chemical (Fatty acids, Mucus and saliva, Cationic antimicrobial peptides)

Front 6

What are the early soluble inflammatory mediators released from local cells?
from plasma?

Back 6

- Bradykinin, Histamine, serotonin, Platelet activating factor, lysosomal enzymes
- Complement (vasodilatation, edema, opsonization)

Front 7

What does bradykinin do

Back 7

Stimulates neutrophil migration, macrophage release of cytokines; induces histamine release; activates complement; vasodilation, pain, edema

Front 8

What does histamine do?

Back 8

Bronchoconstriction, vasodilation, pruritis

Front 9

What does complement do?

Back 9

Vasodilation, edema, opsonization

Front 10

What do lipid mediators do?

Back 10

Cell activation

Front 11

What does platelet activating factor do?

Back 11

Neutrophil recruitment and activation

Front 12

What are the three major C' mediated pathways?
Where do all pathways of complement activation converge?
What cells are activated during the innate immune response?

Back 12

- 1. Alternative pathway (pathogen surface) 2. Lectin pathway (mannose-binding lectins bind to pathogen surface) 3. Classical (Antibody binds to pathogen antigen)
- C3b covalently bound to surface components of pathogen -> innate immune mechanisms
- neutrophils, monocytes/macrophages, mast cells, NK cells

Front 13

Where are two places C' receptors are found?
How does CR1 (complement receptor 1) stimulate phagocytosis?

Back 13

- Neutrophils and macrophages. These facilitate uptake by phagocytosis
- bacterium coated w/complement by alternative and MBL pathways -> C3b binds to CR1 -> C5a activate macrophages -> phagocytose via CR1 (complement receptor =CR)

Front 14

What is def of complement (C')?
What are the two major biologic functions of C'?

Back 14

- a set of plasma proteins that act together to help eliminate extracellular forms of pathogens
- Opsonization and Chemotaxis

Front 15

Which host cells are involved in innate immunity?

Back 15

Neutrophils, Tissue macrophages, mast cells, immature dendritic cells, NK cells, lymphocytes

Front 16

What is the role of neutrophils in innate immunity?

Back 16

Most abundant phagocytes, first cells recruited, relatively short lived

Front 17

What is the role of tissue macrophages in innate immunity?

Back 17

Mature form of monocytes, can undergo division at inflammatory sites, dominant effector cells of the second stage of the innate immmune response, set the stage for adaptive immunity

Front 18

Discuss Mast cells in innate immunity?

Back 18

Located on surfaces (skin, GI tract, respiratory tract, connective tissues); preformed granules of cytokines and histamine; after activation secrete TNF-a, IL-4, IL-5, IL-6, IL-8

Front 19

Which cells are usually first to interact with antigen in the skin and mucosa?

Back 19

Immature dendritic cells

Front 20

What do NK cells express?

Back 20

Inhibitory receptors that recognize MHC class 1. They are thus activated by target cells lacking MHC class 1

Front 21

What do macrophages and mast cells do upon phagocytosis of pathogens in the tissues?

Back 21

Synthesize and secrete a panel of soluble mediators that play a role in the local stimulation of the localized inflammatory response and also have systemic effects

Front 22

What are the major cytokines?

Back 22

IL-1B, TNF-a, IL-6, IL-8, IL-12, Type 1 interferons

Front 23

What does IL-1b do?

Back 23

Activates vascular endothelium, induces the acute phase

Front 24

What does Il-8 do?

Back 24

Chemotactic cytokine

Front 25

What does TNF-a do?

Back 25

Activates vascular endothelium, induces the acute phase response

Front 26

What secretes IL-6?
What does IL-6 do?

Back 26

- macrophages
- Activates lymphocytes;inc Ab production -> fever, induces acute phase ptn prod

Front 27

What secretes IL-12?
What does IL-12 do?
MOA?

Back 27

- macrophages
- Activates NK cells, induce diff of CD4 T cells into TH1 cells
- IL-12 activates NK cells -> cause NK cells to IFN-gamma production

Front 28

What do Type 1 and a/B interferons do?

Back 28

Activate NK cells to kill virus-infected cells

Front 29

What three cytokines induce the acute phase response?

Back 29

IL-1B, TNF-a, IL-6

Front 30

What are acute phase proteins (ACP)?

Back 30

Soluble plasma proteins secreted by hepatocytes in the liver in response to acute infection

Front 31

What two acute phase proteins enhance the fixation of C' at the pathogen surface?

Back 31

C-Reactive protein (binds PC on bacteria) & Mannose-binding protein (MBP)(initiates lectin-binding C' pathway)

Front 32

The process of leukocyte migration to sites of infection is initiated by?

Back 32

Activated tissue macrophages and mast cells at the site of infection

Front 33

Activated macrophages and mast cells at the site of infection causes?

Back 33

Increased vascular permeability, increases in adhesion molecule expression, secrection of cytokines and chemokines

Front 34

What is the multi-step model of leukocyte migration?

Back 34

Rolling of leukocytes on the endothelium, activation of leukocytes, stable adherence to the endothelium, transmigration

Front 35

The process of leukocyte migration to sites of infection is stimulated by?

Back 35

Cytokines, especially TNF-a

Front 36

What are Pathogen Associated Molecular Patterns (PAMPS)?

Back 36

Conserved molecules produced only by microbes and not by the host organism

Front 37

What are Pattern Recognition Receptors (PRR)?

Back 37

A set of germline encoded receptors that recognize PAMPS and thus are specific for non-self structures

Front 38

Name two common PRRs?

Back 38

Toll-like Receptors and Seven transmembrane a-helical receptors

Front 39

Name 4 phagocytic receptors?

Back 39

Mannose receptors, Scavenger receptors, Fc receptors, Mac-1 (integrin)

Front 40

What are two chemicals used to kill microbes?

Back 40

Reactive oxygen intermediates (ROIs) and Nitric oxide (NO)

Front 41

How is NO created in macrophages?

Back 41

The inducible Nitric oxide (iNOS) system

Front 42

What are the four characteristics of inflammation?

Back 42

calor=heat
dolor=pain
rubor=redness
tumor=swelling

Front 43

What are the chemicals produced by the skin to act as barriers to pathogens?

Back 43

- Lysozyme in tears and other secretions, fatty acids, gastric acid

Front 44

The mucosa is an extension of what?
lines the?
primarily composed of?
Forms?

Back 44

- the skin
- digestive tract from mouth to anus
- Epithelial cells
- Physical barrier

Front 45

How are the epithelial cells in the small & large intestine organized?

Back 45

- as villi

Front 46

How do antigens enter the intestine?
MOA?

Back 46

- through M cells
- M cells interspersed between enterocytes and in close contact w/ subepithelial lymphocytes and dendritic cells -> M cells take up antigens from gut lumen by endocytosis -> antigens released beneath M cells -> taken up by APC (dendritic cells)

Front 47

How is the classical pathway initiated?

Back 47

by the binding of either IgM or IgG antibodies to a microbial surface

Front 48

How is the lectin-mediated pathway initiated?

Back 48

by mannose-binding lectin of plasma, which binds to carbs found on bacterial cells

Front 49

How is the alternative pathway initiated?

Back 49

by the local physicochemical environment created by the constituents of some bacterial surfaces.

Front 50

What are the two main MOAs when complement cleaved products (C3a, C4a, C5a) act on blood vessels?

Back 50

- increased permeability -> inc fluid leakage from blood vessels and excavasation of Ig and complement molecules
- inc cell-adhesion molecules -> migration of macrophages, PMNs, and lymphocytes -> microbicidal action of macrophages and PMNs

Front 51

What activates opsonization of neutrophils and macrophages?
What activates chemotaxis of neutrophils and macrophages?

Back 51

- C3b
- C3a, C5a

Front 52

What are usually the first phagocytes that migrate to sites of inflammation?
function?

Back 52

- Neutrophils
- phagocytosis and activation of bactericidal mechanisms.

Front 53

What is the difference between monocytes and macrophages in terms of location and activity?

Back 53

Monocytes are in the blood and are circulating; macrophages are in the tissues and are phagocytosing and killing microorganisms, and activating T cells and initiating immune responses

Front 54

What are the sentinel cells?

Back 54

mast cells and macrophages

Front 55

What is the function of mast cells?

Back 55

expulsion of parasites from body through release of granules containing histamine and other active agents

Front 56

What is the function of NK cells?

Back 56

releases lytic granules that kill some virus-infected cells